Molecular docking study and development of an empirical binding free energy model for phosphodiesterase 4 inhibitors

2006 ◽  
Vol 14 (17) ◽  
pp. 6001-6011 ◽  
Author(s):  
Fernanda G. Oliveira ◽  
Carlos M.R. Sant’Anna ◽  
Ernesto R. Caffarena ◽  
Laurent E. Dardenne ◽  
Eliezer J. Barreiro
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Binding Free Energy ◽  
Docking Study ◽  
Energy Model ◽  
Molecular Docking Study ◽  
Phosphodiesterase 4 ◽  
Phosphodiesterase 4 Inhibitors ◽  
Free Energy Model

scholarly journals Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study

2020 ◽  
Author(s):  
Trina Ekawati Tallei ◽  
Sefren Geiner Tumilaar ◽  
Nurdjannah Jane Niode ◽  
Fatimawali Fatimawali ◽  
Billy Johnson Kepel ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Bioactive Compounds ◽  
Binding Free Energy ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Ligand Complex ◽  
Main Protease ◽  
Glycoprotein Inhibitors

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (Mpro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

scholarly journals In Silico Study on N-Ferrocenylmethyl-N-Phenylpropionohydrazide and N-Ferrocenylmethyl-N-Pheylbenzohydrazide as Anticancer Drugs for Breast and Prostate Cancer

2018 ◽  
Vol 11 ◽  
pp. 17-25 ◽  
Author(s):  
Zegheb Nadjiba ◽  
Boubekri Chérifa ◽  
Touhami Lanez ◽  
Elhafnaoui Lanez
Keyword(s):  
Prostate Cancer ◽  
Free Energy ◽  
Molecular Docking ◽  
Hydrogen Bonds ◽  
Binding Free Energy ◽  
Docking Study ◽  
Dominant Mode ◽  
Molecular Docking Study ◽  
Docking Calculations ◽  
Breast And Prostate Cancer

Molecular docking calculations were used to evaluate the antitumor activities of N-ferrocenylmethyl-N-phenylpropanamide (FP) and N-ferrocenylmethyl-N-pheylbenzohydrazide (FH) against the enzymes of breast cancer 17-beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) and human steroidogenic cytochrome P450 17A1 prostate cancer mutant A105L (CYP17A1). The molecular docking study was performed using the open source AutoDock 4.2 software. The obtained results showed that both FP and FH bind with 17β-HSD1 and CYP17A1 via hydrogen bonds, binding free energy values for the adducts FH-17β-HSD1 and FH-CYP17A1 were respectively equal to-27.67 and-27.55 KJmol-1, while for the adducts FP-17β-HSD1 and FP-CYP17A1 they were respectively equal to-29.13 and 29.18 KJmol-1. The negative values and the magnitude of the obtained binding free energy indicated respectively the spontaneity and the electrostatic interaction of both ligands FP and FH with 17β-HSD1 and CYP17A1 receptors as the dominant mode. Finally the ligand FP binds more strongly to the receptor CYP17A1 and forms two respective hydrogen bonds with Arg96 and His373; this finding clearly indicate that FP is best qualified as potential drug candidature for breast and prostate cancer.

scholarly journals Analysis of flavonoid compounds of Orange (Citrus sp.) peel as anti-main protease of SARS-CoV-2: A molecular docking study

2022 ◽  
Vol 951 (1) ◽  
pp. 012078
Author(s):  
N B Maulydia ◽  
T E Tallei ◽  
B Ginting ◽  
R Idroes ◽  
D N illian ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Binding Free Energy ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Flavonoid Compounds ◽  
Global Pandemic ◽  
Main Protease ◽  
New Type ◽  
The City

Abstract SARS-CoV-2 is a new type of coronavirus that causes COVID-19. This virus was first detected in the city of Wuhan, China, at the end of 2019, and until now, it has become a global pandemic. The FDA recently approved Vekluty (remdesivir) for adults and certain pediatric patients who have COVID-19 and are sick enough to require hospitalization. One of the potential drug target candidates for SARS-CoV-2 is the main protease (Mpro). The purpose of this study was to analyze the flavonoid compounds found in orange (Citrus sp.) peel to determine its potential as anti-Mpro through a molecular docking study. The compounds were initially screened for drug-like properties and then docked using Autodock Vina in the PyRx emulator software. The docking results were visualized using the BIOVIA Discovery Visualizer 2020. The result showed that the binding free energy of hesperidin (-8.6 kcal/mol) was higher than nelfinavir (-8.5 kcal/mol). In addition, hesperitin (-7.3 kcal/mol), sakuranetin (-7.1 kcal/mol), isosacuranetin (-7.2 kcal/mol) and tetra-o-methylscutallerin (-6.8 kcal/mol) exhibited lower binding free energy value than control. Based on these results, hesperidin has the potential as an inhibitor of the main protease’s SARS-CoV-2.

scholarly journals Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study

2020 ◽  
Author(s):  
Trina Ekawati Tallei ◽  
Sefren Geiner Tumilaar ◽  
Nurdjannah Jane Niode ◽  
Fatimawali Fatimawali ◽  
Billy Johnson Kepel ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Bioactive Compounds ◽  
Binding Free Energy ◽  
Biological Activities ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Glycoprotein Inhibitors

Background: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of COVID-19. The search for plant-based antivirals against the SARS-CoV-2 is promising, as several plants have been shown to possess antiviral activities against betacoronaviruses (beta-CoVs) Objective: The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit Main Protease (Mpro) (PDB code: 6LU7) and Spike (S) Glycoprotein (PDB code: 6VXX) of SARS-CoV-2. Methods: Evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. For each compound that was docked, a rule of five was calculated to determine whether a compound with certain pharmacological or biological activities might have chemical and physical properties that would make it an active drug orally in humans. Determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. Results: The results showed that hesperidine, cannabinoids, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and cannabinoids had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Conclusion: Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19.

scholarly journals Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study

2020 ◽  
Author(s):  
Trina Ekawati Tallei ◽  
Sefren Geiner Tumilaar ◽  
Nurdjannah Jane Niode ◽  
Fatimawali Fatimawali ◽  
Billy Johnson Kepel ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Bioactive Compounds ◽  
Binding Free Energy ◽  
Biological Activities ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Glycoprotein Inhibitors

Background: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of COVID-19. The search for plant-based antivirals against the SARS-CoV-2 is promising, as several plants have been shown to possess antiviral activities against betacoronaviruses (beta-CoVs) Objective: The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit Main Protease (Mpro) (PDB code: 6LU7) and Spike (S) Glycoprotein (PDB code: 6VXX) of SARS-CoV-2. Methods: Evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. For each compound that was docked, a rule of five was calculated to determine whether a compound with certain pharmacological or biological activities might have chemical and physical properties that would make it an active drug orally in humans. Determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. Results: The results showed that hesperidine, cannabinoids, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and cannabinoids had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro/3CLpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Conclusion: Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19.

scholarly journals An Antioxidant Potential, Quantum-Chemical and Molecular Docking Study of the Major Chemical Constituents Present in the Leaves of Curatella americana Linn

2018 ◽  
Vol 11 (3) ◽  
pp. 72 ◽  
Author(s):  
Mayara Teles Fujishima ◽  
Nayara Silva ◽  
Ryan Ramos ◽  
Elenilze Batista Ferreira ◽  
Kelton Santos ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Xanthine Oxidase ◽  
Quantum Chemical ◽  
Binding Free Energy ◽  
Chemical Constituents ◽  
Docking Study ◽  
Antioxidant Potential ◽  
Molecular Docking Study ◽  
Hydroalcoholic Extract ◽  
Curatella Americana

Reactive oxygen species (ROS) are continuously generated in the normal biological systems, primarily by enzymes as xanthine oxidase (XO). The inappropriate scavenging or inhibition of ROS has been considered to be linked with aging, inflammatory disorders, and chronic diseases. Therefore, many plants and their products have been investigated as natural antioxidants for their potential use in preventive medicine. The leaves and bark extracts of Curatella americana Linn. were described in scientific research as anti-inflammatory, vasodilator, anti-ulcerogenic, and hypolipidemic effects. So, the aim of this study was to evaluate the antioxidant potentials of leaf hydroalcoholic extract from C. americana (HECA) through the scavenging DPPH assay and their main chemical constituents, evaluated by the following quantum chemical approaches (DFT B3LYP/6-31G**): Maps of Molecular Electrostatic Potential (MEP), Frontier Orbital’s (HOMO and LUMO) followed by multivariate analysis and molecular docking simulations with the xanthine oxidase enzyme. The hydroalcoholic extract showed significant antioxidant activity by free radical scavenging probably due to the great presence of flavonoids, which were grouped in the PCA and HCA analysis with the standard gallic acid. In the molecular docking study, the compounds studied presented the binding free energy (ΔG) values close each other, due to the similar interactions with amino acids residues at the activity site. The descriptors Gap and softness were important to characterize the molecules with antioxidant potential by capturing oxygen radicals.

scholarly journals Synthesis, characterization (IR, 1H, 13C & 31P NMR), fungicidal, herbicidal and molecular docking evaluation of steroid phosphorus compounds

2019 ◽  
Vol 17 (1) ◽  
pp. 621-628 ◽  
Author(s):  
Mahboob Alam ◽  
Youngwon Kim ◽  
Soonheum Park
Keyword(s):  
Molecular Docking ◽  
Binding Free Energy ◽  
Docking Study ◽  
Herbicidal Activity ◽  
Phosphorus Compounds ◽  
Moderate Activity ◽  
Spectroscopic Techniques ◽  
Molecular Docking Study ◽  
Mycelium Growth ◽  
Phosphorus Containing

AbstractPhosphorus containing steroidal derivatives such as 3β-oxo-[diazaphosphalidine-2’-one] stigmast-5-ene and 3β-oxo-[diazaphosphalidine-2’-one] stigmast-5,22-diene were designed, synthesized and characterized using spectroscopic techniques (IR, 1H, 13C & 31P NMR, HRMS) and elemental analysis. The fungicidal and herbicidal studies of the compounds were performed and the experimental outcomes showed that compound 4 showed a good fungicidal activity against mycelium growth of fungi, while in the case of herbicidal activity, both compounds show a moderate activity compared to the commercial drug; Atrazine. The binding free energy of active compound 4 to the receptor named 4-Hydroxyphenylpyruvate dioxygenase (HPPD) was calculated using the molecular docking study. The HPPD is one of the most effective targets of plants for the herbicide study.

scholarly journals Molecular Docking Evaluation of Some Natural Phenolic Compounds as Aldose Reductase Inhibitors for Diabetic Complications

2017 ◽  
Vol 5 (2) ◽  
pp. 135-148 ◽  
Author(s):  
Ajmer Singh Grewal ◽  
Neelam Sharma ◽  
Sukhbir Singh ◽  
Sandeep Arora
Keyword(s):  
Molecular Docking ◽  
Aldose Reductase ◽  
Diabetic Complications ◽  
Binding Free Energy ◽  
Docking Study ◽  
Polyol Pathway ◽  
Binding Modes ◽  
Active Site Residues ◽  
Molecular Docking Study ◽  
Natural Phenols

The enzyme aldose reductase (AR) is a member of aldoketoreductase super-family which catalyzes the formation of sorbitol from glucose through polyol pathway of glucose catabolism. Reduced sorbitol production via polyol pathway due to AR inhibition is a target of choice for controlling major complications of diabetes. Epalrestat is the only commercially available inhibitor of AR till date,thus, there is a great need to search for more economical, nontoxic and safer inhibitors of AR enzyme. Flavonoids,the polyphenol compounds in plants have been reported for inhibitory effects against AR. The objective of this study is to explore the binding modes of naturalphenolic compounds with AR to design safer natural drugs as alternatives to synthetic drugs. We conducted a molecular docking study on some naturalphenolic compounds with AR enzyme in complex with the synthetic inhibitor. The overlay of the docked pose of the selected natural phenols with the ARreference inhibitor complex showed that the selected natural compounds have the similar binding pattern with the active site residues of the enzyme as that of co-crystallized inhibitor. The results of docking study showed the best binding affinity of AR with that of 2-(4-hydroxy-3-methoxyphenyl) ethanoic acid and butein, having the lowest binding free energy of –9.8 kcal/mol and–9.7 kcal/mol, respectively. This information can be utilized to design potent, economical and non-toxic natural AR inhibitors from natural phenols for the therapeutics of diabetic complications.

scholarly journals MOLECULAR DOCKING STUDY BETWEEN 3 THAI MEDICINAL PLANTS COMPOUNDS AND COVID-19 THERAPEUTIC PROTEIN TARGETS: SARS-COV-2 MAIN PROTEASE, ACE-2, AND PAK-1

2021 ◽  
pp. 41-48
Author(s):  
SAFIRA CANDRA ASIH ◽  
RAFIDHA IRDIANI ◽  
MUHAMAD SAHLAN ◽  
MOHAMMAD NASIKIN
Keyword(s):  
Molecular Docking ◽  
Medicinal Plants ◽  
Profile Analysis ◽  
Binding Free Energy ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Protein Targets ◽  
Main Protease ◽  
Docking Approach ◽  
Thai Medicinal Plants

Objective: The present study aimed to evaluate those 3 compounds among 122 Thai natural products by using a molecular docking approach to inhibit Main Protease (Mpro) of SARS-CoV-2 (PDB code: 6Y2F), Angiotensin Converting Enzyme (ACE)-2 (PDB code: 1R4L), and PAK-1 kinase (PDB code: 5DEW). Methods: The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine and interaction profile analysis through 2-dimensional visualization using LigPlot+. The determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). Result: The results of this study indicate that overall, Panduratin A has the best affinity in inhibiting the main protease of SARS-CoV-2, ACE-2, and PAK-1 compared to other compounds. Conclusion: The three thai medicinal plants compound has the potential to be developed as specific therapeutic agents against COVID-19.

scholarly journals Development of SARS-CoV-2 Inhibitors Using Molecular Docking Study with Different Coronavirus Spike Protein and ACE2

2021 ◽  
Vol 1 (1) ◽  
pp. 1-14
Author(s):  
Israa Mohamed Shamkh ◽  
Dina Pratiwi
Keyword(s):  
Molecular Docking ◽  
Host Cell ◽  
Binding Free Energy ◽  
Hydroxypropyl Methylcellulose ◽  
Docking Study ◽  
Cell Receptor ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
Binding Ability ◽  
S Protein

The novel coronavirus SARS-CoV-2 is an acute respiratory tract infection that emerged in Wuhan city, China. The spike protein of coronaviruses is the main driving force for host cell recognition and is responsible for binding to the ACE2 receptor on the host cell and mediates the fusion of host and viral membranes. Recognizing compounds that could form a complex with the spike protein (S-protein) potently could inhibit SARS-CoV-2 infections. The software was used to survey 300 plant natural compounds or derivatives for their binding ability with the SARS-CoV-2 S-protein. The docking score for ligands towards each protein was calculated to estimate the binding free energy. Four compounds showed a strong ability to bind with the S-protein (neohesperidin, quercetin 3-O-rutinoside-7-O-glucoside, 14-ketostypodiol diacetate, and hydroxypropyl methylcellulose) and used to predict its docking model and binding regions. The highest predicted ligand/protein affinity was with quercetin 3-O-rutinoside-7-O-glucoside followed by neohesperidin. The four compounds were also tested against other related coronavirus and showed their binding ability to S-protein of the bat, SARS, and MERS coronavirus strains, indicating that they could bind and block the spike activities and subsequently prevent them infection of different coronaviruses. Molecular docking also showed the probability of the four ligands binding to the host cell receptor ACE2. The interaction residues and the binding energy for the complexes were identified. The strong binding ability of the four compounds to the S-protein and the ACE2 protein indicates that they might be used to develop therapeutics specific against SARS-CoV-2 and close related human coronaviruses.

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